tbuckley/cabot-search huggingface dataset:
Emergence of Responsive Surface‐Enhanced Raman Scattering Probes for Imaging Tumor‐Associated Metabolites (Adv. Healthcare Mater. 12/2022)
Authors: Hang Yin, Ziyi Jin, Wenjia Duan, Bing Han, Limei Han, Cong Li
Journal: Advanced Healthcare Materials (2022)

Stimuli-Responsive Probes Tumor-associated metabolites, the products of metabolic reprogramming in cancer cells, are valuable in timely evaluating tumor occurrence and progress. Article number 2200030 by Limei Han, Cong Li, and co-workers, highlights recent advances in the development of metabolite-responsive SERS probes, discusses the mechanisms leading to the responsive signal, introduces biomedical applications of these SERS probes, and forecasts their challenges and perspectives in clinical translation.
PB2328: CHRONIC LYMPHATIC LEUKAEMIA (CLL) ASSOCIATED TO ACQUIRED FACTOR V INHIBITOR. A CASE REPORT.
Authors: A. Porro Camarero, I. Hernandez de Castro, J. C. Iglesias, P. López de Ugarriza, C. Rodríguez de Miñón, G. Flórez Meana, S. Alonso Álvarez, Á. Bernardo Gutiérrez, I. Soto Ortega
Journal: HemaSphere (2022)

Background: Acquired inhibitors against Factor V (FV) are a very unusual, being its incidence: 0.09-0.29 cases/106 inhabitants/year, although it may be underestimated. A non-negligible percentage of cases are related to autoimmune diseases, pregnancy, malignant diseases, infections, as well as antibiotics and idiopathics causes. FV inhibitors may debut as thrombosis or be discovered incidentally in blood clotting tests. Antibodies against FV are usually IgG-type, although IgM-type may also occur. Management involves both controlling hemostasis and eradication of the inhibitor. Aims: Describe the finding and management of an inhibitor against clotting FV in an CLL diagnosed patient. Methods: Analysis of a clinical case by basic coagulation study, factors dosing by coagulative methods, as well as inhibitors identification by Bethesda tests according to ISTH recommendations. Results: A 83-year-old pluripathologic male was diagnosed of CLL in 2019 as an occasional finding without treatment criteria. CLL progressed through 2020 and is currently in stage C of Binet, RAI 4 with 13q delection (CLL IPI 4 high risk group). During hospital admission due to chronic kidney disease exacerbation he developed an Atrial Fibrillation and initiated treatment with low molecular weight heparin (LMWH). A month after discharge he suffered from severe epistaxis with poor local haemostatic control and an elongation of TTPAr (3.96) was objected. Clotting factors dosage was normal except for FV: 0.10% with a FV inhibitor of 19.45 UB. Corticotherapy was initiated at doses of 1mg/kg plus Cyclophosphamide obtaining the results and progression summarized in Table 1, ending with negativization and obtaining haemostatic levels of FV. Image:Summary/Conclusion: A review of the literature showed that 16% of patients with anti-VF inhibitors had an underlying malignant disease, including haematological diseases such as multiple myeloma, myeloproliferative neoplasms and mantle lymphoma. However, no information has been found on its association with CLL, which presents autoimmune complications in 25% of cases. We expose a case of anti-FV associated to CLL, which after a timely diagnosis and treatment, follows favourable evolution.
PB2186: INTENSITY OF THE CONDITIONING REGIMEN AND TIMING OF AUTOGRAFT ENGRAFTMENT IN PATIENTS WITH MULTIPLE MYELOMA
Authors: I. Kostroma, R. Sabitova, Z. Sidorova, T. Zamotina, S. Gritsaev
Journal: HemaSphere (2022)

Background: One of the ways to increase the intensity of conditioning regimen is the adding of additional drug to melphalan. Supposed that combination of drugs has more potential to reduce the myeloma cells content, which translates into improved progressive-free survival. On the other hand, the development of prolonged cytopenia with extended hospital stay is not exclude. Aims: Comparative assessment of graft engraftment time in patients with multiple myeloma (MM) after autologous stem cell transplantation (AutoSCT) using four conditioning regimens: Mel200, Mel140, melphalan with thiotepa (Mel/Thio) and melphalan with carfilzomib (Mel/Carfil). Methods: The data of 53 patients with MM analyzed. The number of patients who received Mel200, Mel140, Mel/Tio and Mel/Carfil regimens prior to infusion of thawed cell suspension was 24, 13, 10 and 6, respectively. Eleven AutoSCT (20.8%) were the second ones. The conditioning regimen with reduced dose of melphalan (Mel140) was prescribed predominantly for the second transplantation: 6 (46.2%) vs 3 (12.5%) for the first AutoSCT; p=0.022. In the posttransplant period. granulocyte colony-stimulating factor (G-SCF) was received by 20 (83.3%), 12 (92.3%), 8 (80.0%) and 5 (83.3%) patients in the respective groups. Results: The median achievement by the absolute number of neutrophils at the level 0.5x10/9/L and more in the groups was 10 (6-15), 13 (9-19), 10 (9-11) and 14 (10-18) days, respectively. The difference in enraftment time was significant between the Mel/Thio and Mel/Carfil groups; p=0.012. There were no difference in the number of patients with episodes of febrile neutropenia: 6 (25.0%), 2 (15.4%), 3 (30.0%) and 1 (16.7%), respectively. Three (12.5%) patients with Mel200 regimen and 1 (10.0%) patient with Mel/Thio regimen did not have thrombocytopenia below 20x10/9/L. In other patients, the median of reaching platelet level 20x10/9/L and more did not differ: 14 (17-19), 14 (9-19), 13 (10-15) and 15 (12-16) days, respectively. The median number of infused platelets doses did not differ either: 2.5 (1-5), 3 (2-6), 2.5 (1-4) and 2 (1-2), respectively. The length of stay of patients in the hospital from the day of infusion of thawed cell suspension to discharge was as follow: 17.5 (12-21), 19 (14-26), 16 (15-20) and 18 (14-20) days, respectively, differences no. Summary/Conclusion: The intensification of conditioning regimen is haracterized by acceptable toxicity, regardess of the type of drug used, and does not lead to a lengthening of the hospital stay.
HIV Testing Before and During the COVID-19 Pandemic — United States, 2019–2020
Authors: Elizabeth A. DiNenno, Kevin P. Delaney, Marc A. Pitasi, Robin MacGowan, Gillian Miles, Andre Dailey, Cari Courtenay-Quirk, Kathy Byrd, Dominique Thomas, John T. Brooks, Demetre Daskalakis, Nicoline Collins
Journal: MMWR Morbidity and Mortality Weekly Report (2022)

HIV testing is a core strategy for the Ending the HIV Epidemic in the U.S. (EHE) initiative, which has the aim of reducing new HIV infections by at least 90% by 2030.* During 2016-2017, jurisdictions with the highest HIV diagnosis rates were those with higher prevalences of HIV testing; past-year HIV testing was higher among persons who reported recent HIV risk behaviors compared with those who did not report these risks (1). During 2020-2021, the COVID-19 pandemic disrupted health care delivery, including HIV testing in part because many persons avoided services to comply with COVID-19 risk mitigation efforts (2). In addition, public health departments redirected some sexual health services to COVID-19-related activities.† CDC analyzed data from four national data collection systems to assess the numbers of HIV tests performed and HIV infections diagnosed in the United States in the years before (2019) and during (2020) the COVID-19 pandemic. In 2020, HIV diagnoses reported to CDC decreased by 17% compared with those reported in 2019. This decrease was preceded by decreases in HIV testing during the same period, particularly among priority populations including Black or African American (Black) gay men, Hispanic or Latino (Hispanic) gay men, bisexual men, other men who have sex with men (MSM), and transgender persons in CDC-funded jurisdictions. To compensate for testing and diagnoses missed during the COVID-19 pandemic and to accelerate the EHE initiative, CDC encourages partnerships among federal organizations, state and local health departments, community-based organizations, and health care systems to increase access to HIV testing services, including strategies such as self-testing and routine opt-out screening in health care settings.
P1566: PROTON PUMP INHIBITION FOR SECONDARY HEMOCHROMATOSIS IN HEREDITARY ANEMIA, A PHASE III PLACEBO-CONTROLLED RANDOMIZED CROSS-OVER CLINICAL TRIAL
Authors: A. Van Vuren, J. Kerkhoffs, S. Schols, A. Rijneveld, E. Nur, D. Peereboom, Y. Gandon, P. Welsing, R. van Wijk, R. Schutgens, W. van Solinge, J. Marx, T. Leiner, B. Biemond, E. van Beers
Journal: HemaSphere (2022)

Background: Iron overload is a severe general complication of hereditary anemias. Treatment with iron chelators is hampered by important side-effects, high costs and the lack of availability in many countries with high prevalence of hereditary anemias. Aims: To investigate the safety and efficacy of esomeprazole in treatment of iron overload in patients with non-transfusion-dependent hereditary anemias. Methods:Design Phase III randomized placebo-controlled cross-over trial. Setting Enrollment from March 2018 through April 2019 in five centers of expertise in the Netherlands. Participants Thirty adult patients with mild-to-moderate iron overload were enrolled (non-transfusion-dependent thalassemia (N=13), pyruvate kinase deficiency (N=8), congenital sideroblastic anemia (N=3), congenital dyserythropoietic anemia (N=3), sickle cell disease (N=2), and hereditary elliptocytosis (N=1)). Intervention Esomeprazole 40mg twice daily and placebo for 12 months in a cross-over design. Main Outcome and Measure Change of liver iron content measured by MRI. Results: Treatment with esomeprazole resulted in a statistically significant reduction in liver iron content that was 0.55mg Fe/g dw larger than after treatment with placebo (95% CI [0.05 to 1.06]; p=0.03). Baseline liver iron content at start of esomeprazole was 4.99mg Fe/g dw (IQR 3.47; 7.21), versus 4.49mg Fe/g dw (IQR 2.96; 6.35) at start of placebo. Mean delta liver iron content after esomeprazole treatment was -0.57mg Fe/g dw (SD 1.20; N=24) versus -0.11 (SD 0.75; N=23) after placebo treatment. Changes in serum ferritin values were non-significant between treatment arms. Esomeprazole was well tolerated, reported adverse events were mild and none of the patients withdrew from the study due to side effects. Summary/Conclusion: Esomeprazole 40mg twice daily resulted in a significant reduction in liver iron content when compared to placebo in a heterogeneous group of patients with non-transfusion-dependent hereditary anemias with mild-to-moderate iron overload. From an international perspective this result can have major implications given the fact that proton pump inhibitors may frequently be the only realistic therapy for many patients without access to or not tolerating iron chelators. Longer follow-up is needed to see whether this effect will last for a longer period. Trial Registration Netherlands Trial Register NL6659 – PPI in secondary hemochromatosis (www.trialregister.nl).
P1039: PALPABLE SPLEEN SIZE IS PROGNOSTIC IN PRIMARY BUT NOT SECONDARY MYELOFIBROSIS
Authors: M. Lucijanic, I. Krecak, E. Soric, D. Galusic, H. Holik, V. Perisa, M. Moric Peric, I. Zekanovic, R. Kusec
Journal: HemaSphere (2022)

Background: Splenomegaly is a clinical hallmark of primary (PMF) and secondary myelofibrosis (SMF). Although not a part of disease specific risk scores, spleen size represents disease burden and correlates with unfavorable disease features. Spleen size reduction is a function of baseline spleen size and was recently shown to be independent prognostic factor in composite PMF and SMF cohort of ruxolitinib treated patients. Aims: To estimate prognostic properties of palpable splenomegaly and potential differences between PMF and SMF patients. Methods: We analyzed a multicentric cohort of 191 patients from 6 Croatian centers with either PMF or post polycythemia vera (PV) and essential thrombocythemia (ET) SMF diagnosed in period from 2004-2021 who had available data on palpable spleen size. Diagnoses were established according to 2016 and 2008 criteria. Risk was stratified according to the DIPSS in PMF and according to the MySEC-PM in SMF patients. Palpable spleen size was assessed at the time of diagnosis or referral and stratified in three categories: non-palpable, <10 cm and ≥10 cm. Results: A total of 191 patients were analyzed, among them 144 PMF (63 early, 81 overt fibrotic) and 47 SMF (27 post PV; 20 post ET). Median age was 67 years, there were 64% males. Intermediate-2 or high risk disease was present in 45% PMF and 49% SMF patients. Non-palpable spleen, <10 cm and ≥10 cm splenomegaly were present in 31%, 43% and 26% PMF patients, respectively, and 23%, 49% and 28% SMF patients, respectively. Palpable spleen size was similar between patients with PMF and SMF (median 3 vs 4 cm, P=0.325). Patients with palpable spleen ≥10 cm were significantly grouped among patients with higher risk disease in PMF (P=0.026) but not SMF (P=0.654). Degree of bone marrow fibrosis was significantly associated with higher spleen size in PMF (P=0.008) but not SMF (0.809). On the contrary, JAK2 mutational status had no significant association with spleen size in PMF (P=0.847) but was significantly associated with higher spleen size in SMF (P=0.035). Regarding overall survival, larger spleen size was significantly associated with shorter overall survival in PMF (P<0.001) but not SMF (P=0.825) as shown in Figure. Time to thrombosis had no significant association with larger spleen size in neither PMF nor SMF (P>0.05). Time to bleeding was significantly shorter in PMF patients with both <10 cm and ≥10 cm in comparison to non-palpable spleen (P<0.05) whereas palpable spleen size had no significant association with in SMF patients (P>0.05). Image:Summary/Conclusion: Various clinical features are differently associated with palpable spleen size in PMF and SMF patients. Larger spleen size is prognostic of worse survival and higher bleeding risk in PMF but not SMF patients. This might have repercussions on prognostic scores based on palpable spleen size that might differently perform in PMF and SMF patients.
PB1892: IMATINIB RESISTANCE: THE ROLE OF PHARMACOGENETIC VARIABILITY IN A SOUTH AFRICAN COHORT
Authors: C. De Long, F. February, N. Mashigo, F. Bassa, C. Swanepoel
Journal: HemaSphere (2022)

Background: Drug resistant cancers are often associated with poor patient outcomes and burdens an already strained healthcare system. The underlying mechanism of resistance is poorly understood, however Chronic Myeloid Leukemia (CML) serves as a useful disease model. For CML, highly effective therapies have been developed, such as tyrosine kinase inhibitors, particularly the first line drug Imatinib. Unfortunately, approximately 20-30% of patients do become resistant to Imatinib. Variability in patient drug response could be due to single nucleotide polymorphisms (SNPs) in genes that encode for Imatinib-metabolizing enzymes and transporters. Aims: The overall aim of the study is to evaluate the effect selected SNPs located within genes (CYP3A4/3A5 (Cytochrome P450), OATP1A2 (SLCO1A2), OCTN1 (SLC22A4) and hOCT1 (SLC22A1) that encode selected drug transporters has on drug uptake, particularly Imatinib and to determine if these SNPs contribute to an alternative mechanism leading to Imatinib resistance in a South African cohort. Furthermore, the study aims to investigate whether the identified SNPs can serve as biological predictors that will aid in more efficient treatment plans. Methods: A maximum of 44 samples from Imatinib resistant CML patients will be analysed. The patient’s treatment response will be monitored using the GeneXpert and the selected SNPs will be analysed using PCR-based genotyping assays. In addition, 44 non-resistant CML patients will be included as controls. Results: Provisional data for SNPs SLC22A1 (rs628031) and CYP3A4 (rs2740574) suggest that the SNPs are more prevalent in the non-resistant group with 25% and 77.2% of patients having the SNPs opposed to the 7.89% and 68.1% of patients having the SNP in the resistant group, respectively. However, the data should be analysed along with the data of other SNPs in the study to determine poor outcome of imatinib treatment in CML patients. Summary/Conclusion: The anticipated results would aid in determining whether the selected SNPs contributes to Imatinib resistance and to identify potential biological predictors of outcome which could help improve patient treatment stratification.
PB2190: HLA-HAPLOIDENTICAL PERIPHERAL BLOOD STEM CELL TRANSPLANTATION WITH POST-TRANSPLANT CYCLOPHOSPHAMIDE AFTER REDUCED-INTENSITY CONDITIONING
Authors: J. Kim, Y. Park, N. Yun, J.-A. Kim
Journal: HemaSphere (2022)

Background: Allogeneic peripheral blood stem cell transplantation (PBSCT) is a potentially curative treatment for patients with hematological malignancies. However, the availability of HLA-matched, related or unrelated donors is always in question. Haploidentical related donors are alternative donor options for patients who lack an HLA-matched donor but are in urgent need of transplantation. However, haploidentical PBSCT (haploPBSCT) poses significant challenges because of the HLA mismatch, which often increases the risk of graft-versus-host disease (GVHD) and non-relapse mortality (NRM). A recent study led by a group at Johns Hopkins pioneered the use of post-transplant cyclophosphamide (PTCY) in the haploPBSCT setting. In the haploPBSCT, the use of PTCY in combination with tacrolimus and mycophenolate mofetil (MMF) have been found to lower the rates of acute and chronic GVHD, as well as NRM. Aims: We conducted this prospective study to further evaluate the safety and efficacy of PTCy-haploPBSCT. Methods: Eleven patients diagnosed with hematologic disease (AML, ALL, MDS, and aplastic anemia; 4, 1, 4, and 2, respectively) were enrolled in this study. The median age was 44 (range, 24 to 65). The conditioning regimen consisted of fludarabine (150 mg/m2), busulfan (6.4 mg/kg), and total body irradiation (TBI, 3Gy). High-dose cyclophosphamide (50 mg/kg/day on days 3 and 5), cyclosporine, and MMF were used for GVHD prophylaxis. The median numbers of CD34+ cells of PBSCs were 11.6 × 106 /kg (range, 6.1–24.9 × 106 /kg). Results: Overall survival (OS) and relapse-free survival (RFS) at 1-year were 79% and 69%, respectively. Two patients relapsed. One patient was AML and another relapsed with RAEB. Neutrophil engraftment was achieved in 91% of patients with a median of 14 days (range, 13–15 days). The cumulative incidence rates of grades I–IV and III-IV acute GVHD at 100 days were 36% and 9%, respectively. The cumulative incidence rates of mild and moderate chronic GVHD at 1-year were 9% and 18%, respectively. No patients developed severe chronic GVHD. The cumulative incidence rates of NRM, relapse and GVHD-free/RFS at 1-year were 21%, 31% and 62%, respectively. Summary/Conclusion: Our results indicate that PTCy-haploPBSCT is a valid and safe strategy for preventing severe acute and chronic GVHD. In addition, it may also provide better clinical outcomes in long-term disease control. However, our study suggests that relapse still remains as a major cause of treatment failure. Therefore, there is a need for a modified conditioning regimen that can enhance anti-leukemic effects in aggressive diseases such as acute leukemia.
PB1875: TREATMENT OF YOUNGER PATIENTS WITH CHRONIC LYMPHOCYTIC LEUKEMIA IN TUNISIA: FCR STILL STANDARD FOR FIRST-LINE THERAPY
Authors: W. Miled, J. Dorra, K. Rihab, K. Kacem, B. L. Raihane, M. Raoudha, M. Balkis
Journal: HemaSphere (2022)

Background: Chronic lymphocytic leukemia (CLL) is characterized by clonal proliferation and progressive accumulation of B-cell lymphocytes that typically express CD19+,CD5+,and CD23+.Fludarabine,cyclophosphamide and rituximab (FCR) is recommended as first-line therapy for fit patients who are younger than 65 years and have no 17p deletion/ TP53 mutation. Aims: The aim of this study was to analyze the characteristics of CLL in younger patients treated with FCR. Methods: We performed a retrospective study involving young patients with CLL (≤ 65 years old),in the clinical hematology department of Aziza Othmana Hospital,in Tunisia between 2013 and 2020. Patients were considered as fit when CIRS(cumulative illness rating skill) was inferior to six. Results: Seventy-six patients were included(46 males and 30 females).The median age was 56.3 years with a sex ratio of1.53.Seventy-two patients were FIT for chemotherapy. 85.5% had more than one lymph nodes regions affected. Cytogenetics testing were requested for 41 patients of which 42.1% were FISH method. Only 6 patients had 17 p deletion. In the Binet staging system, 40.8% patients were stage A, 27.6% were B and 31.6 % were C. Thirty patients were on therapeutic abstention initially. Five patients received chlorambucil.10 had CLB-Rituximab and 21 had FCR. Fifteen patients treated with FCR were in complete remission (71.4%). Four febrile neutropenia episodes happened, two of them was grade 4. Seven patients had neutropenia grade 3 during minimum one cycle however no infection has occurred. The event free survival was 33.3 months for patients who have been seen regularly. Thirty –nine patients were lost to follow –up; thus, we couldn’t evaluate the event or relapse free survival. Death rate was 7.89% (6 patients of which 3 received FCR). Summary/Conclusion: FCR remains the first-line therapy for fit patients who are younger than 65 years and have no 17p deletion /mutation TP53 in Tunisia.Our patients have a good tolerance to the drugs and few infectious episodes have occurred.